More epidemiologic data are needed on the relation of background-level exposure to man-made chemicals with short half-lives to child development. The embryonic and fetal stages of development are periods of heightened susceptibility to effects of xenobiotics. For xenobiotics with short half-lives, measurement has been a challenge in the past, but new technologies now support better exposure assessment. Multiple urine specimens are frequently the medium of choice for assessing exposure to such agents. Recent data suggest: a) that exposure of pregnant women to background-levels of bisphenol A results in increased risk of pregnancy loss, increased risk of obesity among offspring, and earlier age at menarche among female offspring, b) that background-level of exposure of pregnant women to nonpersistent pesticides can result in reduced birthweight and impaired neurodevelopment in offspring, and c) that background-level exposure to phthalates may be having adverse reproductive effects and increased risk of allergic diseases such as asthma. We seek to increase our capacity to study the relation of background-level exposure to chemicals with short half-lives to pregnancy outcomes and child development. To achieve this goal we are supporting collection of multiple urine specimens during pregnancy in a newly begun cohort, the Generation R study (described below). The plan is to support collection of urine 3 times during pregnancy for the mothers of 2,500 children in the cohort. Generation R is an ongoing prospective study of 10,000 children who will be followed from early fetal life to young adulthood, and aims to study how factors and events during pregnancy and early childhood can affect growth, development, and health in later life. All pregnant women in Rotterdam who expect to give birth between June 2002 and June 2006 are invited to participate, together with their partner. This study has been set up by the Erasmus Medical Center. The multidisciplinary characterization of the cohort, starting in early pregnancy, will produce a database containing biological, medical, genetic, psychological and community-related data which can be used to address a wide spectrum of research questions. The research questions have been subdivided as growth and physical development, cognition and behavior, illnesses and accidents, and utilization of health care resources. The advantage to studying this cohort, e.g., over the Norway Mother and Child Cohort Study, is that we will have multiple urine specimens, including one during the first trimester, enhancing our ability assess exposures, especially during organogenesis. Furthermore, the outcome assessment in the Generation R cohort is more intensive and standardized than in Norway. In February of 2004, NIEHS support enabled an increase in the number of urine specimens collected from each pregnant woman from 1 to 3 (at 12, 20, and 30 weeks of gestation). As each pregnant woman presents for an ultrasound examination of her fetus, she provides a spot urine specimen that is divided into 3 20ml aliquots and frozen at -20o C in polypropylene containers. Two of these aliquots are reserved for collaborative studies with NIEHS. Although our primary interest is in women with a complete set of three urines (1/trimester, n=2,500 planned), for logistic reasons all women presenting for ultrasound provide a urine specimen that is stored. Last year's progress: In the past year we put in place funding for continued collection of urine until the end of enrollment. At this time we have a complete set of 3 urines for about 2,200 women, and anticipate about 2,500 women with a complete set of 3 urines by the end of enrollment. We have had 100 third trimester urine specimens sent to laboratory to check the levels of exposure in this population, and are awaiting results. Assuming that the levels of exposure are interesting, we will put in place a long term contract to support studies that address specific hypotheses.